1. Field of the Invention
The present invention relates to an antibacterial composition for medical use and a process for the preparation thereof. More particularly, the present invention relates to a synergistic composition which comprises 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo (3.2.0)heptane-2-carboxylicacid, 4-4-dioxide[2S-(2.alpha.,5.alpha.)](sulbactam) or pharmaceutically acceptable salts thereof and 6-[D-(-)- .alpha.-(methylene aminophenylacetamido)]-penicillanic acid (methampicillin) or pharmaceutically acceptable salts thereof.
2. Description of the Prior Art
Sulbactam (penicillanic acid 1,1-dioxide) or pharmaceutically acceptable salts thereof are well known in the art as a kind of .beta.-lactamase-resistance antibiotic. Although sulbactam or pharmaceutically acceptable salts thereof alone are a poor inhibitor of .beta.-lactamases, when sulbactam or pharmaceutically acceptable salts thereof are combined with .beta.-lactamase inhibiting antibiotics, the composition exhibits a modest increase in inhibition of the enzymatic hydrolysis of antibiotics [FU, K.P. and NEU, H.C., Comparative Inhibition of .beta.-lactamase by novel .beta.-lactam compounds. Antimicrobial Agents and Chemotherapy 15, No.2, 171-176 (1979)].
Methampicillin and its salts are disclosed in U.K. Patent No. 1,081,093 and have a marked increase in inhibition against gram-positive and gram-negative bacteria.
When the penicillanic acid sulphnone, sulbactam, and an effective amount of clavulanic acid are used with penicillin derivatives, or cephalosporin derivatives, the .beta.-lactamase inhibiting activity thereof exhibits a modest increase in inhibition against Escherichia coli [Greenwood, D. and Eley, A.: In-Vitro evaluation of sulbactam, a penicillanic acid sulfone with .beta.-lactam inhibitory properties. J. Antimicrobial Chemotherapy 10, 117-123 (1982)]
Pharmaceutical compositions comprising .beta.-lactamose inhibitors are disclosed in U.S. Pat. No. 4,503,040. While the compounds are effective in enhancing the activity of B-lactam antibiotics in general, their preferred use is found in their combination with a penicillin or cephalosporin of established clinical utility, viz., amoxicillin, ampicillin, apalacillin, azlocillin, azthreonam, bacampicillin, carbenicillin, carbenicillin indanyl, carbenicillin phenyl, cefaclor, cefadroxil, cefaloram, cefamandole, cefamandole nafate, cefaparole, cefatrizine, cefazolin, cefmenoxime, cefonicid, cefodizime, cefoperazone, ceforanide, cefotaxime, cefotiam, cefotetan, cefoxitin, cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cephacetrile, cephalexin, cephaloglycin, cephaloridine, cephalothin, cephapirin, cephradine, cyclacillin, epicillin, furazlucillin, hetacillin, levopropylcillin, mecillinam, mezlocillin, penicillin G, penicillin V, phenethicillin, piperacillin, pirbenicillin, pivampicillin, sarmoxicillin, sarpicillin, suncillin, talampicillin or ticarcillin, or a pharmaceutically acceptable salt thereof. However, a pharmaceutical composition of sulbactam combined with methampicillin has never been disclosed in the art and also the marked increase in activity of the composition in treating bacterial infections has never been disclosed.